Tetrahedron (2007), 63-7240-45 Concise synthesis of two trisaccharide analogs related to the glycone constituent of Phanoside, a novel insulin releasing natural product ¶ Geetanjali Agnihotri, Pintu Kumar Mandal and Anup Kumar Misra * Medicinal and Process Chemistry Division, Central Drug Research Institute, Chattar Manzil Palace, Lucknow 226001, UP, India Abstract— Two trisaccharides (2 and 3) related to related to the glycone part of Phanoside, an insulin release stimulator have been synthesized in excellent yield. 1. Introduction Diabetes has been classified as insulin dependent (type 1) and non insulin dependent (type 2). Non insulin dependent diabetes (type 2) diabetes is the commonest form of diabetes constituting 90% of the diabetic population. 1,2 Its prevalence in more affluent societies is spectacular and of general concern. 3 It has broken the age barrier and also appears in younger people. Though its management through drugs is possible, drugs come together with serious side effects. Natural products can provide a better alternative as more effective anti-diabetics with less side effects. Recently, it has been reported that Phanoside 4 (1, Figure 1), a natural product isolated from the plant Gynostemma pentaphylum is effective in stimulating insulin release, and is much more potent than well known anti-diabetic drugs, such as sulphonylureas. 4 As claimed in the original report, Phanoside contains a branched trisaccharide glycone consisting of D-glucose, D-rhamnose and D-lyxose. HO O O O O OH OH OH CH 3 HO O HO OH OH O O HO OH 1 2 HO O HO OH OH O OCH 3 HO O O O O OH HO HO H 3 C O OCH 3 HO O O O O OH HO HO H 3 C 3 O H 3 C HO HO OH Figure 1: Structure of Phanoside (1) and trisaccharide analogs of the glycone (2 and 3) However, L-rhamnose is quite abundant in plant natural products and D-rhamnose is occassionally found in the microbial origin. Although the structural elucidation for the presence of D-rhamnose moiety instead of L-rhamnose was not clearly stated in the original paper, we were interested in synthesizing some analogous trisaccharide moieties related to the glycone part of Phanoside containing a L-rhamnose moiety. Oligosaccharides containing D-lyxose are also scarce in nature. In order to understand the role of the glycone part of Phanoside in enhancing the insulin release, it is essential to have higher quantities of several trisaccharide analogs related to the glycone part of Phanoside. Hence it was thought to develop a synthetic route for the synthesis of two trisaccharide analogs (2 and 3) related to the glycone part of Phanoside. 2. Results and discussion The synthesis of target trisaccharide (2) as its 4-methoxyphenyl glycoside is demonstrated in Scheme 1. Treatment of D- lyxose tetraacetate (4) with 4-methoxy phenol in the presence of trifluoromethanesulfonic acid afforded 4-methoxy phenyl glycoside (5). Compound 5 was converted to compound 6 following a sequence of reactions consisting of deacetylation using sodium methoxide, 5 isopropylidenation 6 using 2,2-dimethoxypropane and p-toluenesulfonic acid and benzylation using benzyl bromide under phase transfer conditions. 7 Removal of the isopropylidene group 8 from compound 6 using 80% aq. Keywords: Carbohydrate, glycosylations, natural products, insulin, phanoside. ¶ C.D.R.I communication no. 7049. *Corresponding author. Tel.: +91-522-2612411-18, Ext. 4385; Fax: +91-522-2623405; e-mail: akmisra69@rediffmail.com